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  • The DNA plasma in the vaccine is not integrated, because the gene itself does not replicate, even though there is expression of the antigen that it encodes for.

  • The TB studies have looked at three major forms of Ag-85—A, B, and C—and at different variations of these forms (with and without leaders, etc.). They are just now beginning to work with ESET6, the other major secreted antigen that is believed to provide some protection.

  • It is very difficult to say how soon there might be a vaccine for humans. Work seems to be on track in terms of addressing safety concerns. The biggest unknown is whether they will be allowed to test an IND in healthy humans instead of cancer and HIV patients as is currently the case. A great deal depends on the regulatory agency.

  • The influenza vaccine is the most advanced candidate, even though it may not be the best choice for a DNA vaccine because of antigenic drift. And there are influenza vaccines already, but no vaccines for herpes, HIV, etc.

  • Studies have not been conducted with newborn mice, because of their very small size. Studies have used mice from 3 weeks to aged. There might be some advantage to using this technology for something like a measles vaccine to cover the period of 6 to 12 months, before maternal antibodies decline. But this will not be the first population that a commercial laboratory would focus on because of regulatory problems.

  • Tolerance is unlikely to be a problem unless expression is boosted considerably, or unless the dosage is increased significantly. However, more needs to be known about the phenomenon of tolerance induction.

  • From a safety point of view, it might be desirable to transfect a more differentiated but shorter-lasting cell, such as a dendritic cell, rather than a muscle cell. Researchers will probably continue to explore this question.


Clinicians have noticed that when insulin replacement therapy is begun, it often appears to reverse the disease process. This led to experiments in which non-obese diabetic (NOD) mice were given daily prophylactic doses of insulin at the outset of the inflammatory lesion in the pancreatic islets. The results showed that diabetes is not only preventable, but also reversible. Photomicrographs of the pancreas of an NOD mouse showed some islets that were completely free of lymphocytic infiltration, while others were full of lymphocytes.

This raises the question of mechanism, and one possibility is that of beta cell rest: if the animal receives insulin every day, the islets don’t need to produce it, and the suppressed cells don’t produce autoantigens that are reactive to the immune system. In this case, insulin itself seems to be acting in some speci-


Based on a presentation by Noel Maclaren, M.D.

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